Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia
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|ClinicalTrials.gov Identifier: NCT01807598|
Recruitment Status : Completed
First Posted : March 8, 2013
Results First Posted : January 29, 2019
Last Update Posted : January 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Aggressive Systemic Mastocytosis Mast Cell Leukemia Systemic Mastocytosis||Drug: Brentuximab vedotin||Phase 2|
Brentuximab vedotin is an antibody with a covalently attached toxin. The antibody portion targets the protein CD30 on the surface of cells, and the toxin acts against those cells.
I. To evaluate the response rate to SGN-35 (brentuximab vedotin) in patients with tumor necrosis factor receptor superfamily, member 8 (CD30+) advanced systemic mastocytosis (SM) (ASM or mast cell leukemia [MCL] with or without an associated hematological clonal non-mast cell lineage disease [AHNMD]).
I. To evaluate the tolerability and safety profile of SGN-35 in patients with SM.
II. To evaluate expression of CD30 on neoplastic mast cells before and during therapy with SGN-35.
III. To evaluate changes in mastocytosis related symptom scores and quality of life (QOL) using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).
IV. To evaluate the duration of response (DoR) and time to response (TTR). V. To evaluate progression-free survival (PFS).
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 weeks for 1 year and then every 12 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological Clonal Non-Mast Cell Lineage Disease (AHNMD)|
|Study Start Date :||September 2013|
|Actual Primary Completion Date :||September 2017|
|Actual Study Completion Date :||September 2017|
Experimental: Brentuximab vedotin
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Drug: Brentuximab vedotin
- Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement) [ Time Frame: Up to 1 year ]
Overall response rate (ORR) is sum of complete response (CR); partial response (PR); and clinical improvement (CI) in 1 year, ie, ORR=CR+PR+CI. The outcome is the number of participants without dispersion.
CR is following with response duration(RD) ≥12 weeks (wk)
- No mast cell disease
- Tryptase <20 ng/mL
- Neutrophils ≥1x10e9/L with normal differential
- Hemoglobin ≥11 g/dL
- Platelets ≥100x10e9/L
- No hepatosplenomegaly
- No systemic mastocytosis(SM)-related organ damage PR is following with RD ≥12wk
- Neither CR or progressive disease(PD)
- Neoplastic mast cells reduced ≥50%
- Tryptase reduced ≥50%
- 1+ disease finding resolved CI is following with RD ≥12wk
- Neither CR; PR; or PD
- 1+ of findings above Stable disease (SD) Not CR, PR, Cl, or PD Progressive disease (PD)
- Worsening organ damage
- Doubling of laboratory abnormality
New transfusion dependence of ≥4 units red cells or platelets at 8wk
•+ ≥100% in transfusions for 8wk
- 10-cm+ splenomegaly
- Brentuximab Vedotin Toxicity [ Time Frame: Up to 1 year ]Toxicity was assessed as the number of adverse events considered possibly, probably, or definitely-related to treatment with brentuximab vedotin. The outcome is reported as the total number of related events, a number without dispersion, and the number of related events (without dispersion) considered to be either a hematologic toxicity or non-hematologic toxicity.
- Percent Change of CD30 Expression on Neoplastic Mast Cells [ Time Frame: Baseline and up to 1 year ]The presence of the CD30 marker (epitope) on neoplastic (cancerous) mast cells in core bone marrow biopsy samples was assessed by immunohistochemical methods, before and after brentuximab vedotin treatment. CD30 is a member of the TNF-receptor (TNF-R) superfamily, and is a transmembrane glycoprotein receptor that is normally at very low levels on the surface of activated T-cells. Overexpression of the CD30 marker is indicative of T-cell lymphoproliferative disorders and neoplastic mast cells, and the effect of a particular treatment on CD30 expression may be related to the efficacy of that treatment. The outcome is reported as the median percentage change in the level of CD30 detected, reported with full range.
- Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score [ Time Frame: Up to 1 year ]The clinical effect of patient symptoms associated with systemic mastocytosis or mast cell leukemia were assessed with the patient-reported outcome survey entitled Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms [(MPN-SAF(MCD)]. The MPN-SAF(MCD) is a 36-question survey, with possible responses ranged from 0 to 10, with 0 indicating not present or no effect; 1 meaning present but most favorable; and 10 meaning worst imaginable (least favorable). Total range is 0 to 360, with 0 being best possible, and 360 being worst possible. Total symptom score is calculated as the sum of the individual survey scores reported at baseline and after treatment, with lower numbers indicating less effect, and larger numbers indicated greater effect. The outcome is reported as mean score value with dispersion.
- Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Up to 1 year ]Overall quality of life (QoL) was assessed by a single specific question from the 36-question Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms [(MPN-SAF(MCD)] survey. Possible responses for theQoL question range from 0 to 10, with 0 indicating "as good as it can be" (most favorable), and 10 meaning "as bad as it can be" (least favorable). The QoL score was obtained at baseline and after treatment. The outcome is reported as mean score with dispersion.
- Duration of Response (DOR) [ Time Frame: Up to 1 year ]Duration of response (DOR) is defined as the time from the start of the first confirmed response until the date of the first documented and confirmed disease progression or death due to ASM or MCL. For participants with a confirmed clinical response, the outcome was to be reported as the median DOR with standard deviation.
- Time to Response (TTR) [ Time Frame: Up to 1 year ]Time to response (TTR) is defined as the time from the date of start of treatment to the date of first confirmed response. For participants with a confirmed clinical response, the outcome was to be reported as the median TTR with standard deviation.
- Progression-free Survival (PFS) [ Time Frame: Up to 1 year ]
Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression; death; or initiation of new therapy. The outcome is reported as the mean number of days of PFS, with 95% confidence interval.
Progressive disease (PD) is any of the following:
- Worsening of any organ damage
- Doubling of any laboratory abnormality
- New transfusion dependence of ≥ 4 units red cells or platelets at 8 wk
- ≥ 100% increase in transfusions for 8 wk
- 10-cm+ splenomegaly
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01807598
|United States, California|
|Stanford University, School of Medicine|
|Stanford, California, United States, 94305|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jason Gotlib||Stanford University Hospitals and Clinics|